Estimation of Prevalence of Hospital-Acquired Blood Infections among Patients Admitted at a Tertiary Hospital in Oman over a Period of Five Years: A Cross-Sectional Study

Background Data from developed/developed countries have shown that hospital-acquired blood infections (HA-BSIs) are one of the most severe nosocomial infections and constitute 20%–60% of hospitalization-related deaths. Despite the high morbidity and mortality rates and the enormous burden of health care costs associated with HA-BSIs, to our knowledge, there are few published reports on HA-BSI prevalence estimates in Arab countries, including Oman. Objectives This study aims to explore the HA-BSI prevalence estimates over selected sociodemographic characteristics among admitted patients at a tertiary hospital in Oman over five years of follow-up. The regional variations in Oman were also examined in this study. Methods This hospital-based cross-sectional study reviewed reports of hospital admissions over 5 years of retrospective follow-ups at a tertiary hospital in Oman. HA-BSI prevalence estimates were calculated over age, gender, governorate, and follow-up time. Results In total, 1,246 HA-BSI cases were enumerated among a total of 139,683 admissions, yielding an overall HA-BSI prevalence estimate of 8.9 cases per 1000 admissions (95% CI: 8.4, 9.4). HA-BSI prevalence was higher among males compared to females (9.3 vs. 8.5). HA-BSI prevalence started as relatively high in the group aged 15 years or less (10.0; 95% CI 9.0, 11.2) and then declined as age increased from 36 to 45 years (7.0; 95% CI 5.9, 8.3) when it started to increase steadily with increasing age in the group aged 76 or more (9.9; 95% CI 8.1, 12.1). The governorate-specific estimate of HA-BSI prevalence was the highest among admitted patients who resided in Dhofar governorate, while the lowest estimate was reported from the Buraimi governorate (5.3). Conclusion The study provides supportive evidence for a steady increase in HA-BSI prevalence over age categories and years of follow-up. The study calls for the timely formulation and adoption of national HA-BSI screening and management programs centered on surveillance systems based on real-time analytics and machine learning.


Introduction
Hospital-acquired bloodstream infections (HA-BSIs) are one of the most severe hospital-acquired infections (HAIs) [1][2][3]. Surveys have shown that HA-BSIs were responsible for 20%-60% of hospitalization-related deaths [4,5]. In the United States, HA-BSIs represent 10% of HAIs and have been ranked as the eleventh leading cause of death, with 99,000 deaths annually from 1.7 million, who have contracted HAIs [6]. In some Western European countries, HA-BSIs have been established to trigger high morbidity rates and two-thirds of the annual deaths [7].
Although HA-BSIs are likely to thrive in various geographical and ethnicities around the world, the prevalence of HA-BSIs has been generally reported from the industrialized countries of Northern America, Western Europe, and pocket countries in the Pacifc Rim. It is, therefore, necessary to conduct studies that have documented HA-BSIs in various parts of the world, so that the best practices can be considered globally. Tere is an urgent need to document the pattern of HA-BSIs in emerging economies since most of the global population concentrates on developing countries. Some preliminary data indicate that, in addition to the dearth of studies, those regions appear to have suboptimal patient safety measures, including infection control practices [8,9]. Studies by authors in [10,11] indicated rampant compliance with safety measures. Due to limited resources and safety culture [9], the prevailing health situation in developing countries would appear bleak in the foreseeable future [10]. Terefore, studies on patient safety, including hospital-acquired infections, are needed.
Studies addressing the burden of hospital-acquired infections, including the prevalence of HA-BSIs and its microbial pathogens in developing countries, are critical to contemplate preventive measures. Among the developing countries in the Middle East and North Africa, some studies have started to quantify the burden of BSI [8,10,12,13]. In the Gulf Cooperation Council (GCC), some studies have emerged on various aspects of HA-BSIs [11,[14][15][16][17][18].
To our knowledge, in Oman, previous reports have suggested that HA-BSIs may be prevalent in Oman, including multidrug-resistant organisms [19][20][21][22][23][24]. Tis study aims to explore (i) the sociodemographic characteristics of the patients who have had HA-BSI and (ii) the prevalence of HA-BSI, and the regional distribution and pathogens associated with the HA-BSI.

Study Design.
To achieve the stated objectives, an ambidirectional, hospital-based, cross-sectional study of HA-BSIs has been undertaken at Sultan Qaboos University Hospital (SQUH) for fve years, from January 2015 to 2019. SQUH is a 570-bed tertiary care teaching hospital in Muscat, Oman, receiving its referrals from regional, secondary, and primary healthcare centers in seven governorates (i.e., Muscat, Batinah, Dakhiliyah, Sharqiya, Dhofar, Dhahirah, and Buraimi). Te hospital includes an Infection Control Unit consisting of doctors and nurses specialized in infection control-related disciplines.

Case Defnition and Ascertainment.
Te CDC defnition and classifcation of BSI and HA-BSI were adopted [25]. Terefore, BSI was diagnosed by one positive blood culture, if the isolate is a recognized pathogen, one blood culture from the central line, or at least two blood cultures from the peripheral line if the isolate is one of the common commensals. BSI cases were classifed as hospital-acquired cases if the laboratory-confrmed bloodstream infection occurs after 48 hours or more of hospital admission. Te study included all adults and children, patients, and newborns with HA-BSI during the study period. Newborns with HA-BSI less than 48 hours of delivery were also included in the study. Te situation in which BSI occurred due to earlier admission, and the patient was discharged not more than 48 hours after the last admission, was also considered as HA-BSI.

Data Collection.
Te data were collected by reviewing patient medical records on the hospital information system (HIS). Te data collected included sociodemographic data, clinical information, and microbiological information. Two clinical investigators developed and employed a coding guide based on the International Statistical Classifcation of Diseases and Related Health Problems (ICD) criteria. Tey reviewed and scored all evaluations to determine if the HA-BSI labeling was consistent with the standard international diagnostic criteria of BSI.
Te inter-rater reliability among the two clinical investigators culminated in 94% agreement on the overall HA-BSI case status. For ongoing inter-rater reliability checks, a random sample of records (10%) was scored independently by a reviewer with clinical experience in the management of HA-BSI and did not participate in the diagnostic reviews. Te percentage agreement between the raters on the fnal HA-BSI case defnition was 96%.

Statistical Analysis.
A general analysis strategy has been formulated to follow which was described by Alsumait et al. [26] and Nguyen [27]. Te prevalence of HA-BSI in patients was calculated by dividing the number of HA-BSI cases by the total admission. Te prevalence of HA-BSI isolates was calculated by dividing the number of HA-BSI isolates by the total admission. Prevalence was reported per 1,000 admissions. Te 95% confdence intervals (95% CI) of prevalence estimates were calculated using the Poisson distribution method of binomial variables. A P value of 0.05 or less was considered statistically signifcant. Statistical Package for Social Sciences (SPSS) (version 24.0, IBM) was used for all statistical analyses. Ethical approval for this study was obtained from the Medical Research Ethics Committee at the College of Medicine and Health Sciences, Sultan Qaboos University. Table 1 shows the distribution of the selected sociodemographic and clinical characteristics of admissions enrolled in the study. Tere were 139,683 admissions, of which 1246 (0.89%) were HA-BSI cases. Admitted male patients were slightly higher (71,823; 51.4%). More than half (58.6%) of the admissions were patients aged below 45. Over the years, there has generally been a steady distribution of total admissions. Most admitted patients (34.7%) were residents of Muscat Governorate, followed by Batinah and Dakhiliyah (18.5% and 13.7%, respectively). Table 1 also compares the selected characteristics among HA-BSI cases versus noncases. Te gender distribution was similar around 50% among both groups. HA-BSI cases tended to be younger in age. Te distributions of each governorate of residence and year of procedure request were comparable among HA-BSI cases and noncases. In all comparisons, the diferences were not statistically signifcant (p > 0.05). Table 2 and Figure 1 show the prevalence of HA-BSI among admitted patients and in isolates, by the year of admission. Te overall prevalence of HA-BSI among admitted patients was 8.9 (95% CI 8.4, 9.4) cases per 1,000 admissions, while the overall prevalence of HA-BSI among isolates was 11.5 cases (95% CI 10.9, 11.0) per 1,000 admissions. Overall, there has been a slight decrease in the prevalence of HA-BSI patients and isolates during the period from 2015 to 2019. In addition, the prevalence estimates of the isolates were greater than those of the cases over the years of admission. Table 3 and Figure 2 illustrate the seasonal trend of the occurrence of HA-BSI throughout the year, stratifed by the month of admission. Te prevalence of HA-BSI cases and isolates was steady from January to May. In June, the prevalence increased and continued to fuctuate until the end of the year. Te highest prevalence was observed in August (11.0; 95% CI 9.1, 13.2), while the lowest prevalence was observed in July (7.8; 95% CI 6.4, 9.5). Table 4 shows the frequency and prevalence estimates of HA-BSIs among admitted patients stratifed by age and gender. Te HA-BSI prevalence per 1000 admissions among males (9.3; 95% CI 8.6, 10.0) was higher than that among females (8.5; 95% CI 7.9, 9.3). Te age-specifc prevalence estimates indicated that the HA-BSI prevalence estimates started relatively high in the group aged 15 years or less (10.0; 95% CI 9.0, 11.2), and then declined as age increased from 36 to 45 years (7.0; 95% CI 5.9, 8.3) then it started to increase steadily with increasing age in the group aged 76 or more (9.9; 95% CI 8.1, 12.1). Figure 3 depicts the distribution of HA-BSI prevalence estimates over increasing age categories. Figure 4 depicts the distribution of gender-specifc prevalence estimates over increasing age categories. HA-BSI prevalence among males was proportionately higher than that among females in all age categories. HA-BSI prevalence among males started high among patients aged 15 years or less. It then declined gradually till the age category 36 to 45 years , and then it started to increase steadily, reaching the highest estimate among people aged 70 or older. Te HA-BSI prevalence among females appears to follow a steadier pattern over all age categories.

Discussion
In a hospital setting, the presence of immune-compromised patients, the lack of vigilance to hygiene, and the inherent tendency of medical and surgical procedures to encroach on natural protective barriers in the human body all can trigger the proliferation of spreading pathogens. Some developed

Interdisciplinary Perspectives on Infectious Diseases
Tis study was performed to determine the prevalence of HA-BSI in a tertiary care hospital in Oman. Te overall prevalence rates of HA-BSI per patient and isolates were 8.9 per 1000 admissions and 11.5 per 1000 admissions, respectively. Similar studies were conducted in the USA and Europe, and slightly lower readings were obtained [28]. A Chinese surveillance study reported a prevalence rate of 5.7/ 1000 admissions in a traditional Chinese medicine hospital [29]. Our prevalence rate mimics the results obtained from other studies conducted in other developing countries such as Saudi Arabia, Jordan, and Qatar (8.5, 8.1, and 7.8 per 1,000 admissions, respectively) [10,30].
Tis study also solicited the monthly fuctuation in the rate of HA-BSIs, but the trend was generally steady. Te    Interdisciplinary Perspectives on Infectious Diseases   Interdisciplinary Perspectives on Infectious Diseases isolates' overall prevalence rate was generally higher than that reported from North America and Western Europe [28]. According to our study, the prevalence rate of HA-BSIs fuctuated over age categories. Te pattern obtained could be interpreted by the strength of the immune system. Te immunity starts low when the baby is born and then increases as the age increases to a certain point. After that, immunity declines as age advances, rendering the body more susceptible to infection. Te exciting part came when the age and gender-specifc prevalence rate was tested. It showed that the prevalence rate of HA-BSI was greater in males than in females in each age group. Moreover, it revealed that age signifcantly afects the prevalence rate among males more than females. Te prevalence rate among females seems steady over diferent age categories. A study carried out in Tailand has pointed to the age-gender-specifc incidence rate of HA-BSI, and it found that the incidence rate of HA-BSI was higher in males than in females (0.8 vs. 0.6 per 1,000 patient days, IRR 1.2; 95% CI; 1.13 to 1.30, P < 0.001) [31].
Among HA-BSI cases in this study, males (53.5%) were insignifcantly more than females (46.5%) (P � 0.16). Te overall prevalence rate of HA-BSIs is slightly higher among males than in females (8.5 vs. 9.2 per 1,000 admissions). About a quarter of the total number of cases fall in the age group (0-15) years, in which the prevalence rate is higher than the other age groups (10.0 per 1000 admissions). In a similar study carried out in the New York city, HA-BSI was signifcantly associated with males (OR � 1.25, P < 0.001) and with patients in age categories 65-84 and >85 (OR � 1.12 and 1.37, respectively) [32]. A Swedish study found that males constitute 59% of HA-BSI cases (P < 0.001) [33].
Te HA-BSI acquired in the intensive care unit (ICU) was a signifcant consequence of critical illness (K. B. Laupland et al., 2006). In this study, HA-BSI was more prevalent among patients admitted to the ICU (43.5 per 1000 admissions) compared to other hospital wards. Te obtained prevalence rate was comparable to that reported in Australia (52 per 1000 ICU admissions) [34,35]. Tis fnding was much lower than that in Egypt, where the prevalence rate of HA-BSI was 75 per 1000 ICU admissions [36]. In Belgium Ghent University Hospital, the prevalence of HA-BSI among patients older than 45 years was 27.7 per 1000 ICU admissions from 1992 to 2006 [37]. In our study, most HA-BSI cases were reported in the medical ward (42.37%). Tis fnding was comparable to the result obtained in Qatar, where the percentage was 49.5%. Our fnding, however, was considerably higher than the results obtained in similar studies in Saudi Arabia, where HA-BSI cases from medical wards constitute 14.6% of the total cases [11,14,15].
In a recent study, the ICU came second after the medical ward by a percentage of 24.1, less than the percentages obtained in Qatar and Saudi Arabia (33.3% and 53.2%, respectively). It has been found that about a quarter of HA-BSI cases were in pediatric patients. Tis fnding does not support Qatari (3.8%) and Saudi Arabian (4.8%) studies. Te results from pediatric wards in the Qatari study and the Saudi study are converging, indicating better infection control measures in this ward. Te percentages of HA-BSI cases reported in surgical wards were 9.1 and 3.2 in Qatar and Saudi Arabia, respectively. In our study, the percentage reported in the surgical ward is 10.9%. Tus, it is highly comparable to studies in Saudi Arabia [15,16,18].

Limitations.
Tis study has some limitations, and it is worthwhile to highlight here. First, a nonprobability sampling method (convenience sampling) was used to collect the data from one hospital; hence, the results cannot be generalized to the whole country. Second, the relatively small sample size may have also afected the power of the study to detect signifcant diferences. Not all observations were statistically signifcant across categories in the data analysis. Finally, since the study was cross-sectional, the HA-BSI occurrence indices were limited to prevalence only over retrospective follow-up, which implied a lack of temporality and potentially reversed causality. Incidence parameters would have been better measures of HA-BSI occurrence because they establish temporality.

Conclusion
In summary, this hospital-based, cross-sectional study explored the variation in the prevalence of HA-BSI among admitted patients in a tertiary hospital in Oman over fve years of retrospective follow-up. Te study provides supportive evidence for a slow reduction in HA-BSI prevalence over age categories and years of follow-up. It depicts the variety of gender-specifc CRC prevalence estimates over increasing age categories. Te study calls for the timely formulation and adoption of national HA-BSI screening programs geared toward increasing awareness of HA-BSI and considering screening as primary prevention to respond to the increase in HA-BSI prevalence in Oman and other Arab countries.

Data Availability
Te data used to support the fndings of this study are available from the corresponding author upon request (ymfarsi@squ.edu.om).